This study was designed to determine the feasibility of administering high dose intensive chemotherapy for patients with advanced diffuse histiocytic lymphomas using measures to prevent infection. Patients with diffuse histiocytic lymphoma who were found to be stage III or IV after appropriate staging techniques were placed in reverse isolation in a laminar air flow unit and begun on oral non-absorbable antibiotics. They then received high dose chemotherapy with cyclophosphamide 1500 mg/sq.m IV day one, adriamycin 60 mg/sq.m IV day one, vincristine 1.4 mg/sq.m IV days one and eight and a ten day course of oral prednisone at 40 mg/m sq.m. Eight patients were treated. Myelosuppression was the most frequently noted toxicity and though often severe was brief. Results show four complete responses, one partial response and three failures. There have been three deaths of those patients achieving complete response, however. One patient died from adriamycin cardiotoxicity, one from disseminated fungemia and one patient with renal failure. The patient who has achieved a partial remission achieved a complete remission on further therapy. Although the results of this study indicate that high dose chemotherapy with these agents is effective at achieving complete responses, the toxicities of this approach appear prohibitive.